When ultraviolet radiation reaches the skin, melanocytes are activated to promote the synthesis of melanin, and this melanin has a function of defending the skin against the harmful ultraviolet radiation. However, the synthesis of melanin leads to tanning of the skin, and if the metabolism of the skin is deteriorated, there occurs deposition of pigment, and formation of pigment spots which are cosmetically troubling. Therefore, there is a demand for a model which can be used for research on the pigmentation system in the skin, or for the evaluation of a lightening agent for suppressing pigment spot formation or removing pigment spots.
As the model for the evaluation of skin pigment spots, a three-dimensionally cultured skin, a brownish guinea pig, a C57 black mouse, a hairless SKH-2 mouse, and the like have been reported (Imokawa, G., Kawai, M., Mishima, Y., and Motegi, I. (1986) Differential analysis of experimental hypermelanosis induced by UVB, PUVA, and allergic contact dermatitis using a brownish guinea pig model. Arch. Dermatol. Res. 278, 352-362.; Welsh, B. M., Mason, R. S., and Halliday, G. M. (1999) Topical all-trans retinoic acid augments ultraviolet radiation-induced increases in activated melanocyte numbers in mice. J. Invest. Dermatol. 112, 271-278.; Kawaguchi, Y., Mori, N., and Nakayama, A. (2001) Kit(+) melanocytes seem to contribute to melanocyte proliferation after UV exposure as precursor cells, J. Invest. Dermatol. 116, 920-925.; Seiberg, M. (2001) Keratinocyte-melanocyte interactions during melanosome transfer, Pigment Cell Res. 14, 236-242.).
The three-dimensionally cultured skin contains human-derived melanocytes and epidermal cells innoculated on a support corresponding to dermis, such as collagen or the like, and it is also commercially available (Seiberg, M. (2001) Keratinocyte-melanocyte interactions during melanosome transfer. Pigment Cell Res. 4, 236-242.).
However, with regard to the three-dimensionally cultured skin, it is necessary to perform research under a presumption that the cultured skin clearly differs from the actual skin, and there is a problem that the evaluation is possible only for about 2 weeks at maximum.
Furthermore, in an animal model, since the finding that when ultraviolet radiation (UVB) is irradiated to brownish guinea pigs which have melanocytes present in the epidermis like humans, pigmentation is formed (Arch Dermatol Res 278:352-362, 1986), and research using the brownish guinea pigs have been actively conducted (Hachiya, A., Kobayashi, A., Ohuchi, A., Takema, Y., and Imokawa, G. (2001) The paracrine role of stem cell factor/c-kit signaling in the activation of human melanocytes in ultraviolet-B-induced pigmentation. J. Invest. Dermatol., 116, 578-586.).
Also, for the hairless SKH-2 mouse and the like are known and used as a model for ultraviolet-induced pigmentation in addition to brownish guinea pigs (Welsh, B. M., Mason, R. S., and Halliday, G. M. (1999) Topical all-trans retinoic acid augments ultraviolet radiation-induced increases in activated melanocyte numbers in mice. J. Invest. Dermatol. 112, 271-278).
However, since the genetic information of the brownish guinea pig has not been known yet, when attempting to interpret the function of a factor, it is required to verify every time as to whether or not a gene probe or an antibody used in other species could be used, and perform the interpretation. Also, the hairless SKH-2 mouse has problems, when compared with humans, that the thickness of the epidermis is obviously different, and the like.
Because of the above reasons, the creation of a model in which the pigmentation system of the human skin, particularly formation of pigment spots, is simulated faithfully and maintained stably for a long time, is desired.